Document Detail


PRAK is essential for ras-induced senescence and tumor suppression.
MedLine Citation:
PMID:  17254968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Like apoptosis, oncogene-induced senescence is a barrier to tumor development. However, relatively little is known about the signaling pathways mediating the senescence response. p38-regulated/activated protein kinase (PRAK) is a p38 MAPK substrate whose physiological functions are poorly understood. Here we describe a role for PRAK in tumor suppression by demonstrating that PRAK mediates senescence upon activation by p38 in response to oncogenic ras. PRAK deficiency in mice enhances DMBA-induced skin carcinogenesis, coinciding with compromised senescence induction. In primary cells, inactivation of PRAK prevents senescence and promotes oncogenic transformation. Furthermore, we show that PRAK activates p53 by direct phosphorylation. We propose that phosphorylation of p53 by PRAK following activation of p38 MAPK by ras plays an important role in ras-induced senescence and tumor suppression.
Authors:
Peiqing Sun; Naoto Yoshizuka; Liguo New; Bettina A Moser; Yilei Li; Rong Liao; Changchuan Xie; Jianming Chen; Qingdong Deng; Maria Yamout; Meng-Qiu Dong; Costas G Frangou; John R Yates; Peter E Wright; Jiahuai Han
Related Documents :
16762148 - Fibroblast-like synoviocytes from patients with rheumatoid arthritis are more sensitive...
17237388 - The b cell antigen receptor controls ap-1 and nfat activity through ras-mediated activa...
12470828 - Replicative senescence of human fibroblasts: the role of ras-dependent signaling and ox...
14602078 - Coactivation of stat and ras is required for germ cell proliferation and invasive migra...
10066798 - Pp60(v-src) induction of cyclin d1 requires collaborative interactions between the extr...
9746348 - Direct effects of corticotrophin on oral keratinocyte cell proliferation.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell     Volume:  128     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-26     Completed Date:  2007-03-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295-308     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. pqsun@scripps.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Aging / genetics*
Cell Line
Cell Transformation, Neoplastic / genetics,  metabolism*
Cells, Cultured
Gene Expression Regulation, Neoplastic / genetics
Humans
Intracellular Signaling Peptides and Proteins
Mice
Mice, Knockout
Phosphorylation
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Signal Transduction / genetics
Skin Neoplasms / chemically induced,  genetics,  metabolism*
Tumor Suppressor Protein p53 / genetics,  metabolism
Tumor Suppressor Proteins / genetics,  metabolism*
p38 Mitogen-Activated Protein Kinases / genetics,  metabolism
ras Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
AI041637/AI/NIAID NIH HHS; AI054696/AI/NIAID NIH HHS; CA106768/CA/NCI NIH HHS; CA91922/CA/NCI NIH HHS; GM67101/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; EC 2.7.1.11/MAP-kinase-activated kinase 5; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.6.5.2/ras Proteins
Comments/Corrections
Comment In:
Cell. 2007 Jan 26;128(2):233-4   [PMID:  17254959 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.
Next Document:  FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis.